Translational Systems Pharmacology Studies in Pregnant Women

Quinney, Sara K.; Gullapelli, Rakesh; Haas, David M.

doi:10.1002/psp4.12269

Cited by 7 publications

(9 citation statements)

References 97 publications

(217 reference statements)

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“…However, these models have complexity, and the omics data and other clinical data in pregnancy may not be available to integrate into these models. 67 Current Knowledge Gaps to Be Addressed to Advance Modeling of PK in Pregnancy. Literature reports indicate that the use of PBPK models in pregnancy has been steadily increasing.…”

Section: Data Interpretation and Translation Into Dosing Recommendati...mentioning

confidence: 99%

“…Although both PBPK and QSP models integrate genomics, transcriptomic, proteomic, metabolomic, PK, PD, and clinical characteristics in maternal, placental, and fetal system, the emerging QSP models can potentially incorporate relatively more mechanistic details that are intended to predict the PD and clinical efficacy in pregnancy. However, these models have complexity, and the omics data and other clinical data in pregnancy may not be available to integrate into these models 67 …”

Section: Considerations For Conducting Clinical Studies In Pregnant I...mentioning

confidence: 99%

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Pharmacokinetic Evaluation in Pregnancy—Current Status and Future Considerations: Workshop Summary

Guinn

Şahin

Fletcher

et al. 2023

The Journal of Clinical Pharma

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As pregnant individuals have traditionally been excluded from clinical trials, there is a gap in knowledge at the time of drug approval regarding safety, efficacy, and appropriate dosing for most prescription medications used during pregnancy. Physiologic changes in pregnancy can result in changes in pharmacokinetics that can impact safety or efficacy. This highlights the need to foster further research and collection of pharmacokinetic data in pregnancy to ensure appropriate drug dosing in pregnant individuals. Therefore, the US Food and Drug Administration and the University of Maryland Center of Excellence in Regulatory Science and Innovation hosted a workshop on May 16 and 17, 2022, titled “Pharmacokinetic Evaluation in Pregnancy.” This is a summary of the workshop proceedings.

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Section: Data Interpretation and Translation Into Dosing Recommendati...mentioning

confidence: 99%

Section: Considerations For Conducting Clinical Studies In Pregnant I...mentioning

confidence: 99%

Pharmacokinetic Evaluation in Pregnancy—Current Status and Future Considerations: Workshop Summary

Guinn

Şahin

Fletcher

et al. 2023

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…8 As a deeper understanding is gained of systems biology, much more intensive study will be possible of the impact of genetic polymorphisms on clinical outcomes and of the interaction of medications with complex systems such as the microbiome. Additionally, until recent advances in computing, 9 the complex biological relationship between mother and fetus was beyond the scope of deep study. Thus, we can expect a new era of understanding of the biological effects of medications and the relationships between these effects and clinical outcomes.…”

Section: The Current State Of Using Bd To Evaluate Pediatric Medicatimentioning

confidence: 99%

Big Data in the Assessment of Pediatric Medication Safety

et al. 2020

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Big data (BD) in pediatric medication safety research provides many opportunities to improve the safety and health of children. The number of pediatric medication and device trials has increased in part because of the past 20 years of US legislation requiring and incentivizing study of the effects of medical products in children (Food and Drug Administration Modernization Act of 1997, Pediatric Rule in 1998, Best Pharmaceuticals for Children Act of 2002, and Pediatric Research Equity Act of 2003).There are some limitations of traditional approaches to studying medication safety in children. Randomized clinical trials within the regulatory context may not enroll patients who are representative of the general pediatric population, provide the power to detect rare safety signals, or provide long-term safety data. BD sources may have these capabilities. In recent years, medical records have become digitized, and cell phones and personal devices have proliferated. In this process, the field of biomedical science has progressively used BD from those records coupled with other data sources, both digital and traditional. Additionally, large distributed databases that include pediatric-specific outcome variables are available. A workshop entitled "Advancing the Development of Pediatric Therapeutics: Application of 'Big Data' to Pediatric Safety Studies" held September 18 to 19, 2017, in Silver Spring, Maryland, formed the basis of many of the ideas outlined in this article, which are intended to identify key examples, critical issues, and future directions in this early phase of an anticipated dramatic change in the availability and use of BD.

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“…18 QSP models have been able to fill in knowledge gaps in certain difficult-to-study populations including various rare diseases 19,20 and neurological disorders including Parkinson disease and Alzheimer disease. [21][22][23] Recently, Quinney et al 24 have addressed the application of QSP in pregnancy and have illustrated the approach and the benefit, although there are still few published examples of the approach applied to investigational drugs in pregnancy. What is clear from the existing published uses cases thus far is that the inputs for development of QSP models to study pharmacotherapy in pregnancy thus far are largely taken from mainstream drug development of the agent in question and seldom vetted against any data in pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Opportunities for Systems Biology and Quantitative Systems Pharmacology to Address Knowledge Gaps for Drug Development in Pregnancy

Barrett

Azer

2023

The Journal of Clinical Pharma

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Pregnant women are still viewed as therapeutic orphans to the extent that they are avoided as participants in mainstream clinical trials and not considered a priority for targeted drug research despite the fact that many clinical conditions exist during pregnancy for which pharmacotherapy is warranted. Part of the challenge is the uncertain risk potential that pregnant women represent in the absence of timely and costly toxicology and developmental pharmacology studies, which only partly mitigate such risks. Even when clinical trials are conducted in pregnant women, they are often underpowered and absent biomarkers and exclude evaluation across multiple stages of pregnancy where relevant development risk could have been assessed. Quantitative systems pharmacology model development has been proposed as one solution to fill knowledge gaps, make earlier and perhaps more informed risk assessment, and design more informative trials with better recommendations for biomarker and end point selection including design and sample size optimality. Funding for translational research in pregnancy is limited but will fill some of these gaps, especially when joined with ongoing clinical trials in pregnancy that also fill certain knowledge gaps, especially biomarker and end point evaluation across pregnancy states linked to clinical outcomes. Opportunities exist for further advances in quantitative systems pharmacology model development with the inclusion of real‐world data sources and complimentary artificial intelligence/machine learning approaches. The successful coordination of the approach reliant on these new data sources will require commitments to share data and a diverse multidisciplinary group that seeks to develop open science models that benefit the entire research community, ensuring that such models can be used with high fidelity. New data opportunities and computational resources are highlighted in an effort to project how these efforts can move forward.

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Translational Systems Pharmacology Studies in Pregnant Women

Cited by 7 publications

References 97 publications

Pharmacokinetic Evaluation in Pregnancy—Current Status and Future Considerations: Workshop Summary

Pharmacokinetic Evaluation in Pregnancy—Current Status and Future Considerations: Workshop Summary

Big Data in the Assessment of Pediatric Medication Safety

Opportunities for Systems Biology and Quantitative Systems Pharmacology to Address Knowledge Gaps for Drug Development in Pregnancy

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